The specific aims of this proposal are as follows: 1) To construct a cDNA library from the mRNAs of a number of homozygous lymphoblastoid cell lines and clone full-length cDNA copies in E. coli, to sequence the cDNA inserts and from them deduce the amino acid sequences of a number of HLA-A, -B, and -C antigen alleles; 2) To isolate genomic clones from human genomic libraries established from homozygous lymphoblastoid cell lines and to analyze these genomic clones and their flanking regions, to study expression of the genomic clones in several systems with a view to using this technique in identification of the clones; 3) To attempt to obtain cDNA clones corresponding to the heavy and light chains of HLA-DR antigens and of the human equivalent of the murine TL and Qa antigens; 4) To study at the genetic level the relationship between a number of human diseases and particular antigens in the HLA region, particularly ankylosing spondylitis (HLA-B27, hereditary hemochromatosis (HLA-A3), multiple sclerosis (HLA-DR), juvenile onset diabetes (HLA-DR3 and 4) and rheumatoid arthritis (HLA-DR4).